4种大鼠肾草酸钙结石模型的比较

目的筛选简便、快捷、成石效果好的SD大鼠肾草酸钙结石的造模方法。方法分别采用目前普遍使用的2种大鼠肾草酸钙结石的模型复制方法和2种改良的造模方法进行造模,并设立空白对照组,造模结束后采集每组大鼠24h尿量及血清,比较大鼠24h尿量、尿Ca2＋、尿Mg2＋、尿pH、尿草酸（0x）及血尿素氮（BUN）、肌酐（cr）、P、Ca2＋、Mg2＋,肾脏病理切片HE染色后光学显微镜下观察和比较各组大鼠肾脏病理改变及草酸钙结晶的沉积情况。结果E组[1％乙二醇＋2％氯化铵＋10％葡萄糖（48d）]在光学显微镜下草酸钙结晶沉积较传统组C组明显增多（P〈0．05）,但有30％大鼠死亡,血肌酐在5组大鼠中最高。D组[1％乙二醇＋2％氯化铵＋10％葡萄糖（28d）]较传统组C组草酸钙结晶沉积明显增多（P〈0．05）,并且造模时间短,大鼠存活率高（80％）,E组与D组相比结晶形成量无统计学意义（P〉0．05）,B组[1％乙二醇（28d）3肾脏中无肾结晶形成,仅有轻微的肾脏病理学改变,大鼠无死亡,肌酐不高。空白对照组无结晶形成,无病理改变。结论用1％乙二醇＋2％氯化铵＋10％葡萄糖诱导28天复制肾草酸钙结石模型的效果好,并且花费时间短,大鼠存活率高,建议选用。     

α-亚麻酸抑制大鼠肾草酸钙结晶形成的实验研究

目的　比较α 亚麻酸和亚油酸预防结石形成的作用。　方法　雄性Wistar成年大鼠 6 0只 ,分 4组 ,每组 15只。C组和D组分别以苏子油 (含α 亚麻酸 6 3% )或葵花籽油 (含亚油酸 70 % ) 2g/d灌胃 4周后 ,用诱石剂 1%乙二醇 (EG)加 1%氯化氨喂饮 ,同时继续以苏子油或葵花籽油灌胃 ,3周后检测各组大鼠肾功能、2 4h血尿生化指标和肾草酸钙结晶情况。仅饮用诱石剂 (B组 ,成石组 )大鼠和正常喂养 (A组 ,空白对照组 )大鼠作对照。　结果　苏子油组肾组织水肿较轻 ,肾内草酸钙结晶数及肾钙含量明显低于成石组 (P <0 .0 1) ,2 4h尿钙排泄、血尿素氮、肌酐浓度显著低于成石组 (P <0 .0 5 ) ,尿肌酐排泄增加 (P <0 .0 5 )。葵花籽油组仅血尿肌酐较成石组明显改善 (P <0 .0 5 ) ,其他指标与成石组差异无显著性意义 (P >0 .0 5 )。　结论　α 亚麻酸能有效改善肾功能 ,减少尿钙排泄 ,抑制实验鼠肾草酸钙结晶形成 ,在尿石症防治方面可能有一定应用价值。     

生骨再造散对激素性股骨头坏死家兔血脂的影响

目的：研究生骨再造散对激素性股骨头坏死家兔血脂水平的影响。方法：家兔45只,随机分为5组;空白对照组、模型组、生骨再造散组、生骨再造散加手术组和马氏补骨片组。用糖皮质激素造成家兔激素性股骨头缺血性坏死模型。造模6周开始,生骨再造散和骨再造散加和术组灌胃生骨再造散（3．2g.kg^-1.d^-1);马氏补骨片组灌注胃马氏补骨片（0．6g.kg^-1.d^-1);空白对照对照组和模型且灌胃等容量生盐盐水。于造模型等5周和给药第5周测各组家兔的胆固醇,甘油三酯和高密度脂蛋白。结果模型组与空白对照组相比,血清胆固醇、甘油三酯明显升高（P＜0．01）,高密度脂蛋白明显降低（P＜0．01）;三个治疗组与模型组比较,血清胆固醇、甘油三酯明显降低（P＜0．05）,高密度脂蛋白明显升高（P＜0．05）;生骨再造散两组与马氏补骨片组比较无显著性差异。结论：生骨再造散对股骨头坏死的治疗作用可能与其对血脂的调节作用有关。     

左归丸对5/6肾切除大鼠IL-1β、p65及胸主动脉钙化的影响

目的:观察左归丸对5/6肾切除大鼠IL-1β、p65及胸主动脉钙化的影响。方法:SPF级Wistar雄性大鼠予以5/6肾切除并给予高磷饮食造模，造模大鼠分为模型组、左归丸组，并同时设空白对照组。术后空白对照组予以普通饮水，模型组和左归丸组予以高磷饮水。术后4周空白对照组和模型组给予灭菌注射用水灌胃，左归丸组行左归丸水溶液灌胃，共8周。灌胃8周后处死大鼠，检测血清BUN、Scr、IL-1β,免疫组化检测胸主动脉IL-1β、p65表达，von kossa染色观察胸主动脉钙化情况。结果:给药8周后，空白对照组和左归丸组BUN与模型组比较，差异有统计学意义(P<0.05)。空白对照组和左归丸组Scr与模型组比较，差异有统计学意义(分别为P<0.01,0.05)。空白对照组和左归丸组IL-1β与模型组比较，差异有统计学意义(P<0.01)。空白对照组大鼠各组IL-1β、p65在动脉血管壁几乎无表达，模型组大鼠表达明显，左归丸组大鼠与空白对照组比较增加，但明显少于模型组；von kossa染色观察空白对照组大鼠胸主动脉中内膜层无明显钙盐沉积，模型组大鼠主动脉钙盐沉积明显，左归丸组...     

药用醋膏预防大鼠泌尿系结石形成及其机制的初步研究

目的:通过应用药用醋膏喂养泌尿系结石模型大鼠,观察大鼠肾组织病理变化及测定肾组织草酸和钙离子含量,观察醋酸预防泌尿系结石的效果,进一步探讨其机制。方法:将适宜体重的健康Wister大鼠随机分为空白组、1%乙二醇+2%氯化铵诱石液造模对照组、30g/100ml高剂量醋膏+1%乙二醇+2%氯化铵诱石液组、10g/100ml低剂量醋膏+1%乙二醇+2%氯化铵诱石液组,喂养28天后处死,取肾组织HE染色,观察草酸钙结晶面积分布情况,测定各组大鼠肾组织中草酸与钙离子含量。结果:空白组与其它三组比较,肾组织草酸钙结晶面积分布及草酸和钙离子含量差异均有统计学意义(均P0.05);造模对照组与高剂量醋膏组比较,肾组织草酸钙结晶面积分布及草酸和钙离子含量差异均有统计学意义(P0.05),而与低剂量醋膏组比较,肾组织结晶面积分布及草酸和钙离子含量差异均无统计学意义(P0.05);高剂量醋膏组与低剂量醋膏组比较,肾组织草酸和钙离子含量差异有统计学意义(P0.05),肾组织草酸钙结晶面积分布差异无统计学意义(P0.05)。结论:在正常食用剂量范围内,高剂量醋膏对大鼠泌尿系结石的形成有预防作用,可降低肾组织中草酸及钙离子含量。     

SAHA对草酸钙肾结晶小鼠肾功能的影响

目的:建立草酸钙肾结晶小鼠模型,探讨辛二酰苯胺异羟肟酸(suberoylanilide hydroxamic acid,SAHA)对模型小鼠肾功能的影响。方法:将24只C57BL/6雄性小鼠随机分为4组:空白对照组(无任何处理)、模型组(NS组)和干预组(DMSO、SAHA/DMSO组);NS组:50 mg/kg的生理盐水(NS)+100 mg/kg乙醛酸盐;DMSO组:50 mg/kg的DMSO+100 mg/kg乙醛酸盐;SAHA组:50 mg/kg的SAHA/DMSO+100 mg/kg乙醛酸盐;实验组分别预先予以NS、DMSO、SAHA 50 mg/kg等量腹腔注射,6 h后三组均给予100 mg/kg的乙醛酸盐腹腔注射,连续给药7 d后处死全部小鼠。在光镜下观察各组小鼠肾组织切片中草酸钙结晶的分布,比较钙盐沉积百分比;检测各组小鼠的血肌酐(血Scr)、血尿素氮(BUN),尿损伤因子1(尿KIM-1),尿钙/尿肌酐比值;检测肾组织的过氧化氢酶(CAT)、维生素E(VE)的含量或活力;并且对肾组织切片TUNEL染色及其半定量分析,比较肾小管凋亡细胞的表达情况。结果:(1)SAHA减少草酸钙肾结晶的形成;(2)SAHA减少模型小鼠的血肌酐、血尿素氮生成,降低尿KIM-1水平;(3)SAHA调节氧化应激水平;(4)SAHA组小鼠的肾小管细胞凋亡减少。结论:本项研究结果证实SAHA可改善草酸钙结晶小鼠的肾功能,减少肾小管细胞凋亡。     

改良大鼠脊髓损伤模型椎管开窗方法的实验研究

目的 探讨新型改良大鼠脊髓损伤模型椎管开窗方法的实用性.方法 将40只普通级成年SD(Sprague-Dawley)大鼠按照随机数字表法分为两组:传统组(20只,采用传统蚕食法椎管开窗进行造模)、改良组(20只,采用椎板揭盖开窗法进行造模),比较两组切口长度、手术时间、术中出血量及术后死亡率,并于术后不同时间点评价两组大鼠运动功能(basso beattie bresnahan,BBB)评分及HE染色结果判定脊髓功能障碍及造模成功与否.结果 切口长度、手术时间、出血量及术后28 d死亡率的比较,改良组明显优于传统组,差异均有统计学意义(均P<0.05).两组大鼠术后BBB评分及HE染色结果提示以椎板揭盖开窗法制备大鼠脊髓损伤模型成功率与传统方法比较,差异无统计学意义(P>0.05).结论改良大鼠脊髓损伤模型椎板开窗相较传统椎管开窗方法有明显的优势,可广泛运用于脊髓损伤基础研究的模型制作.     

多因素所致IgA肾病模型大鼠血清炎症因子水平和肾组织免疫相关蛋白表达的变化

目的通过多因素所致IgA肾病(IgA nephropathy,IgAN)大鼠模型,观察大鼠血清炎症因子以及肾组织T细胞免疫球蛋白黏蛋白-1(T cell immune globulin sticky protein 1,TIM-1)和转化生长因子-β1(transforming growth factor-β1,TGF-β1)的表达变化,探讨IgAN的炎症免疫机制。方法取20只SPF级雄性SD大鼠,采用随机数字表分为模型组和空白对照组。模型组予以牛血清白蛋白溶液(400 mg/kg,1 mL/100g)隔日灌胃,持续6周;皮下注射蓖麻油0.5 mL+四氯化碳溶液0.1 mL,每周1次,持续9周;并给予脂多糖(LPS)溶液(0.05 mg/只),分别于第6、8周尾静脉注射。空白对照组予以等体积纯化水隔日灌胃,相同时间点皮下注射0.9%氯化钠溶液0.4 mL/只和尾静脉注射0.9%氯化钠溶液0.2 mL/只,造模时间为10周。造模后,检测两组大鼠尿微量白蛋白,24 h尿蛋白定量及肝、肾功能指标;采用ELSIA法检测大鼠血清中IgA、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)的含量及肾脏组织中TGF-β1和TIM-1的表达。结果造模后第8周,大鼠出现不同程度的毛色灰暗、精神萎靡、便溏等症状。与空白对照组比较,模型组大鼠尿微量白蛋白和24 h尿蛋白定量显著升高(P0.05);血清IgA含量和肾组织的IgA荧光表达均显著升高(P0.05)。与空白对照组比较,模型组大鼠的血清IL-4、IL-6水平显著增高(P0.05),肾组织的TGF-β1和TIM-1表达显著增强(P0.05)。结论多因素所致IgAN模型和临床IgA患者体征相似,其发病机制和炎症因子释放与TGF-β1及TIM-1的表达密切相关。     

改良式十二指肠空肠转流术动物模型的建立与评价

建立SD大鼠改良式十二指肠空肠转流术(DJB)模型,探讨其对正常大鼠体重的影响。将35只8周龄200~250g健康雄性SPF级大鼠随机分为3组,改良式DJB组15只,假手术组20只分为2个亚组,即饮食控制组10只和空白对照组10只。改良式DJB组行改良式DJB手术,饮食控制组给予饲料量与改良式DJB相同,空白对照组足量饲料,观察记录各组每周进食量及体重变化。改良式DJB组大鼠死亡4只,存活率73.3%。空白对照组与饮食控制组体重均上升,改良式DJB组在术后第1周体重下降,以后体重逐渐增加,但仍低于其他两组(P0.05)。SD大鼠改良式DJB手术模型是稳定、可行的,能有效减缓大鼠体重增长速度。     

无肾功能损伤大鼠肾草酸钙结石模型的筛选

目的 用最小的肾脏功能损伤筛选制作短时、经济和成石效果好的大鼠肾草酸钙结石模型.方法 将雄性SD大鼠90只随机分为两组.实验1采用1.0％氯化铵和不同浓度乙二醇(EC,0.1％、0.2％、0.4％、0.8％)处理.实验2单用不同浓度EG(0.1％、0.2％、0.4％、0.8％)处理.7～21 d后处死大鼠,测体质量、血、尿肌酐和尿草酸盐含量.苏木素-伊红(HE)染色观察肾组织病理改变及肾成石.结果 实验1中,不同浓度EG+ 1.0％氯化铵处理7d后,大鼠尿草酸盐排泄量均高于对照组(P＜0.05).用0.4％或0.8％ EG+ 1.0％氯化铵处理14d后,大鼠肌酐清除率均低于对照组(P＜0.01);光镜观察,肾皮质、髓质和肾乳头等处出现草酸钙结晶体,肾组织炎性损伤加重.实验2中,用0.4％或0.8％ EG处理7d后,尿草酸盐排泄量高于对照组(P＜0.01),但肌酐清除率变化差异无统计学意义(P＞0.05).光镜观察,肾皮质及间质未出现明显水肿,可观察到少量结石结晶但无炎性细胞浸润.结论 单用EG处理大鼠可以在没有严重肾损伤的情况下构造短时、经济和成石效果好的大鼠肾草酸钙结石模型.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.